German Chancellor Angela Merkel regrets Italian Prime Minister Matteo Renzi's decision to resign after his defeat in a referendum on constitutional reform but pledged to work with Italy's next government.

Many investors are looking to Merkel for leadership in Europe, fearing instability could reignite a sovereign debt crisis at a time when the EU is struggling with Britain's decision to leave and support for populist or right-wing parties is on the rise.

"The Chancellor has taken note of the resignation of the Italian Prime Minister with regret," said German government spokesman Steffen Seibert.

He said Merkel had a good relationship with Renzi, marked by deep trust, but the democratic decision of voters had to be respected.

"The German government will offer close cooperation in friendship and partnership with the successor government in Italy, whatever it looks like," Seibert added at a government news conference.

He declined to draw any parallels between the Italian referendum result and the Brexit vote in June and the election in the United States of Donald Trump as the next President.

Foreign Minister Frank-Walter Steinmeier, a member of the Social Democrats (SPD) who share power with Merkel's conservatives, was more blunt, saying he was disappointed by the Italian result.

"This is a government crisis, not a state crisis. It is not the demise of the Western world but it is not a positive contribution in the midst of our crisis situation in Europe," he said through a spokeswoman.